Looking for some suggestions on hacks to resolve what appears to be a heart/brain dilemma associated with apoE4 allele?
Experimenting on myself as safer/quick guinea pig for my father. He has been lifelong sufferer of minor Essential Tremor, but neurodegeneration accelerated rapidly following heart bypass surgery nearly 4 years ago. ET got bad enough that he chose to have a Deep Brain Stimulation implant ~12 months after heart surgery. Neurodegeneration continued resulting in falls, muscle weakness, etc. and a likely diagnosis of a 'Parkinsonism' called Progressive Supranuclear Palsy.
Long journey since <12 mos ago my father's supposedly positive blood work with 'great' LDL = 27 mg/dL just sounded like an anomalous clue when I learned that he started Lipitor for the first time following heart surgery. Found my way through all the statin skeptic literature (e.g. Graveline, Seneff, Deans) where it became very clear to me that cholesterol depletion was a very plausible cause of the overall rapid neurodegeneration. Should probably note here that I also stopped Lipitor immediately upon realizing this about 9 months ago.
About 9 months ago, due to serendipity alone (sequenced family genes as 'gift' for son studying biochemistry undergrad), we discovered that both my father and myself are carriers of a single apoE4 allele, which many of you here know has a large impact on lipid transport and metabolism. This gave me understanding of not only the potential cause of the problem, but led me to believe that by hacking my own health I can come up with recommendations for my dad (to at least arrest the decline). I've finally convinced him to get off the g****mn Lipitor so save his brain and not worry about his heart.
Following clues from books, scientific papers, and web sluthing (thanks esp AHS for bringing so many clues to one place!), I've been drifting to paleo diet for ~ 6months and presently largely paleo plus some 'safe' carbs (a-la Jaminet). Especially since cutting out wheat totally about 3 months ago (thanks Dr. Davis), I quickly lost 15 unnecessary lbs (although never heavy), and frankly feel much better than I have in decades (age 50).
I managed to find cholesterol numbers for both myself and my father from just prior to beginning Lipitor at a time where we were both likely eating a fairly typical American diet. Baseline numbers were very similar...
Self: TC=205, LDL=125, HDL=37, TriG=216
Father: TC = 196, LDL=118, HDL=30, TriG=240
FWIW, 2 other number sets maybe have clues...
Father on on 40 mg/d Lipitor: TC=129, LDL=27, HDL=45, TriG=258
Self on Pritikin (mid 90's): TC=184, LDL=127, HDL=36, TriG=106
From all of my reading, I had formed a hypothesis that my low-carb/high fat diet should have a large effect on my own cholesterol profile: (a) LDL likely up in count, (b) HDL up, (c) TriG's down, and (d) presence of LDL pattern A (i.e. large and fluffy). I also hypothesized e) low CRP. Got VAP test results yesterday from samples taken last Friday (some risk of Thanksgiving cheats?), but indeed I got positive confirmation of a, b, and c, but d (most important) is mixed, and e (CRP) not clear as follows:
Total LDL = 194
LDL4 = 34.6
LDL3 = 100.7
LDL2 = 22.7
LDL1 = 21.9
LP(a) = 5
IDL = 9
Pattern = A/B
Total HDL = 47
HDL2 = 8
HDL3 = 39
Total VLDL = 21
VLDL1+2 = 9.3
VLDL3 = 11
Total Cholesterol = 262
TriG = 97
Remnant Lipoproteins = 20
apoB = 136
apoA1 = 146
CRP = .78 mg/L
So overall, positive news of impact of diet on HDL (except maybe not enough HDL2?) and TriG (clear benefit of low carb), but mixed results in the A/B news on LDL particle size (with full caveats re Masterjohn's warnings on VAP size accuracy).
Although I feel great, my sense is that this profile is not super-healthy yet. From both prior Pritikin diet and Paleo today clear that cutting carbs cuts TriG's. But referencing the banter between Dr's Kruse and Davis in Trackyourplaque comments in August, simply cutting out fats doesn't seem right either. I tend to agree with dr. Kruse because the logic of Seneff that high absolute cholesterol is actually neuroprotective for APOE4's makes sense (i.e. because by body sucks at transporting lipids across BBB, I need more lipid in my blood). But for best heart health, feels like I need to increase the size of those LDL particles?
So, I think my question to the Paleohack community is... as APOE4, since I want plenty of cholesterol in my blood for brain health, but I want that cholesterol to have a heart-healthy profile, what other hacks should I try to improve my own cholesterol profile? ...such that if I achieve success I can give clear and simple recommendations to help my Dad.
Thanks hackers for any suggestions!
It is not that DR.Davis is incorrect but the litmus is that it is VERY RARE at TrackYourPlaque for heart plaque regression. One has to ask WHY?????!! wtf why???
Clearly the low chol, low sat fat, high canola/n-6 PUFA and high doses of pharmaceuticals at the website and advocated by the cardiologist have factors in this. I was 2 yrs at the site and case after sad, pathetic case of PROGRESSION every year is evidence to me that low chol, low sat, high canola/n-6 and pharmaceuticals are not recipes for success. For apoE4, FHC, or anybody with a risk factor for heart disease (which is nearly everyone since it is either #1 or #2 killer in the world).
Seth on the other hand consumes an insane amount of butter (pastured, high in K2, cholesterol and sat fat), low carb, pork belly and fermented foods and flaxseed/oil.
I have a couple posts on apo E4 (google animal pharm apo e4) -- I entirely agree with Kruse. low carb, high fat are the way to go, esp if someone is a carrier for an E4 allele or both (!!) which is/are the least agriculture/carb tolerant folks.
Also please check out by my buddy Jonathon Carey Tripleyourhdl.com (he presented a poster at AHS) -- he is heteroxygous for FHC (familial hypercholesterolemia) with premature death all over his family tree. He is doing wonderfully and no evidence of heart disease on a low carb, high saturated fat + fiber diet. His blog reports his IBS is cured (guar gum).
if you cut saturated fat from diet, you are preventing the immune system and the brain from growing and being maintained at its optimum. The proble with trackyourplaque is that it is very heavy on things proven in medical literature that promote braing and heart degeneration:
-low cholesterol diet because cholesterol is the precursor of neurons, cell membrane and cell to cell communication, and all of our sex and vit D hormones and cortisol
-high canola oil (omega six) which causes rampant inflammatory disease
-low saturated fat because saturated fatty acids are necessary for PPAR and HDL2 and large buoyant pattern A
would love to hear your dad's progress in the future.
I've recently learned I'm APOE4/3 and so this is an interesting question for me.
Not really new in this forum, but maybe improved CRP is more critical for ApoE4 through better omega-6:omega-3 ratio, exercise, and stress management.
ApoE4 carriers have a higher risk of Alzheimer’s and dementia, and they have a higher risk of heart disease. And you know, the conventional view is that they have that higher risk because of higher levels of LDL, but actually the most recent research and our recent understanding of what causes both Alzheimer’s and heart disease suggests that the reason they have a higher risk is that ApoE4 carriers are more susceptible to oxidative damage and inflammation, and it’s the oxidation of the LDL particle that’s the common thread in both increased risk of heart disease and increased risk of Alzheimer’s and dementia. So this ApoE4 mutation that helps dark-skinned people produce vitamin D and also lighter-skinned people in northern latitudes produce enough vitamin D wouldn’t have been a problem in an environment where oxidative risk factors were low, like people weren’t smoking, they were getting plenty of exercise, their stress levels were managed, they weren’t eating a lot of omega-6 polyunsaturated fat that has the potential to oxidize. But in this modern world where the modern lifestyle is full of oxidative risk factors, then this ApoE4 mutation has a dark side. So I just find it fascinating. I mean, it’s like our genetic code is doing the best that it can to make us healthy and protect us from harm, but the lifestyle that we’re living keeps kind of throwing a monkey wrench in the plan.
This article had some interesting info, even though there was some convention wisdom to sift through. And I would have liked to see other healthy population examples than Pima Indians, which are not in my near ancestry. One interesting thing is Pima Indians had high trigs and overweight BMI: "Their age was 38+/-17 years and the BMI 25.7+/-4.5 kg/m2. Plasma cholesterol, triglycerides, LDL C and HDL C were 165+/-29.6, 126+/-83, 98+/-26 and 42+/-12.7 mg/dl respectively."
Conclusion – A Healthy Redox Balance Should Allow Carriers of ApoE ε4 to Benefit from Omega-3s A number of studies have shown that the APOE ε4 allele does not promote cardiovascular disease or dementia progression in individuals in developing countries
The Moreno paper you and Grace discussed was pretty interesting, too. It was counter-intuitive that CHO had the best LDL-size at 26.47 vs. SFA 26.38, MUFA 26.26? Though lower HDL and small sample size.
Russ Dec 6 at 13:13:
Grace, Read the 2004 Moreno paper you linked on LDL Size, Diet, and APOE. Quite good - thanks. Once again clear that carbs are particularly bad for APOE4's. I am somewhat intrigued by Table 5 that shows avg LDL size is higher for APOE3/4's compared to 3/3's and 3/2's regardless of diet?
I wonder the significance to the decreased bile acid synthesis and if it's beneficial to improve that? Plus the faster LDL clearance for apoE4 seemed counter-intuitive, as well.
The apoE4 variant has been associated with increased LDL production from VLDL, increased uptake of postprandial lipoproteins, increased intestinal absorption of cholesterol, decreased bile acid synthesis, and faster LDL clearance from plasma compared with the apoE3 or apoE2 variants (6–8).
I hope you know that folks with higher than CW total cholesterol live longer than those with low cholesterol. 262 is great. Lowering total cholesterol starves the brain of vital cholesterol since the brain is made up of around 63% cholesterol. It is insanity to take statins.
Your Triglycerides are too high...down under 60 acceptable, but lower is better.
Your HDL at 47 is low. Should be above 60 and higher is better.
You have about 50/50 large bouyant to small dense LDL which is headed in the right direction.
Continue on with paleo/primal. If you follow Dr Kruse's Leptin Reset Protocol you will change your LDL particle size to mostly large bouyant pattern A and you will raise your HDL and lower your Triglycerides. Use copious amounts of coconut oil for you and your dad. Lots of animal protein. 70% fat, 20% animal protein, 10% tubers and green veggies without nightshades with coconut oil is a heart healthy, artery and vein strengthen protocol that will heal the leaky gut syndrome that most everyone has that is not paleo.
You do the Reset Protocol and you will feel very well very soon.
I don't have an answer for you, Russ, but I appreciate your question and hope to see the braintrust here pitch in and give you some good info. This is simply my way of bringing your question back up to the top of the board.